The present invention relates to a short efficient enantioselective synthesis of the orally active a antiestrogen of the formula I or XIV ##STR2##
or a pharmaceutically acceptable salt thereof.
The synthesis and the antiestrogenic activity of the compound of formula 1, i.e., (S)-7-hydroxy-3-(4'-hydroxyphenyl)-4-methyl-2-(4"-[2'"-(1-piperidino)-etho xy]phenyl)-2H-benzopyran 4',7-bistrimethylacetate, is disclosed in J. Med Chem., 1997, 40, 2117-2122. See also U.S. Pat. Nos. 5,395,842, and 5,407,947 and J. Med. Chem., 1990, 33, 3216-3222. Each of the synthetic schemes disclosed is a laboratory scale procedure involving costly steps not suitable for a practical commercial scale process.
There is a need for a short, efficient, enantioselective synthesis suitable for the large scale manufacture of the compounds of formulas I and XIV.